Acute Myocardial Infarction, Non ST Elevation Myocardial Infarction, PreDiabetes, ST Elevation Myocardial Infarction
Conditions
Brief summary
Prediabetes is associated to an increased risk of cardiovascular disease and mortality. Although metformin can delay progression to diabetes there is a lack of RCTs evaluating the effect of metformin on cardiovascular outcomes. MIMET aims to investigate if addition of metformin to standard care has effects on the occurrence of cardiovascular events after acute myocardial infarction in patients with newly detected prediabetes (identified by oral glucose tolerance test, HbA1c or fasting glucose levels).
Detailed description
The study is a national multicenter R-RCT associated to the The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART registry) where participants, after informed consent, will be randomly assigned to either open treatment with standard care + metformin or standard care alone in a 1:1 ratio. Standard care consists of diet and life-style advice according to national guidelines but does not include metformin. Baseline data for individual patients will be collected from the SWEDEHEART registry. Patients will be followed per routine care at 2 and 12 months post index AMI and in addition at a final study visit at 24 months. Laboratory measurements and collection of SAE will be performed yearly. In total n=5150 patients is expected to be followed for major CV event (all-cause mortality, myocardial infarction, heart failure and stroke) by linkage with SWEDEHEART and national health registries.
Interventions
DRUGMetformin
Individualised target dose of 2000 mg daily depending on tolerability.
Sponsors
Capio Sankt Görans Hospital
Uppsala University
The Swedish Research Council
Karolinska Institutet
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
I. AMI II. Swedish citizens with a personal ID number ≥18 years and ≤80 years III. Newly diagnosed prediabetes: 1. HbA1c 42-47 mmol/mol or 2. Capillary or venous fasting plasma glucose concentration 6.1-6.9 mmol/L or 3. 2-hour post-load capillary glucose concentration 8.9-12.1 mmol/L or 4. 2-h post-load venous plasma glucose concentration 7.8-11.0 mmol/L 5. HbA1c \<48 mmol/mol and 2-hour post-load capillary glucose concentration \>12.1 mmol/L or 2-h post-load venous plasma glucose concentration \>11.0 mmol/L (thus elevated 2-hour glucose levels in the diabetes range but without HbA1c levels diagnostic for diabetes) IV. Naïve to metformin and other glucose lowering therapy V. Signed informed consent
Exclusion criteria
I. Type 1 diabetes II. Known type 2 diabetes III. Indication for glucose lowering treatment IV. Acute condition with high risk for volume depletion, circulatory shock, hypoxia V. Serious illness, other than cardiovascular, with short life expectancy VI. Renal failure (eGFR \<60ml/min) VII. Hepatic failure VIII. Malignancy within the last year IX. Contraindication or hypersensitivity to the study drug X. Alcohol or drug abuse XI. Pregnancy or breastfeeding XII. Women of childbearing potential without adequate anticonception during any part of the study period XIII. Previous hospitalisation for lactic acidosis XIV. Predicted inability to comply with the study protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to major CV event | Estimated follow-up for each patient is 1-4 years | Major CV event; a composite endpoint of first of all-cause death or main diagnosis of MI, heart failure or stroke (reported in SWEDEHEART, the National Patient Register and the Cause of Death Register). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospitalisation with MI | Estimated follow-up for each patient is 1-4 years | Time to readmission for MI. Hospital admission for MI during day 0-30 after index AMI will be excluded |
| New cancer diagnosis | Estimated follow-up for each patient is 1-4 years | Time to new cancer diagnosis defined as the first occurrence of any cancer in the National Patient Register |
| Initiation of any glucose lowering therapy | Estimated follow-up for each patient is 1-4 years | Time to initiation of any glucose lowering therapy (ATC code A10 in the Prescribed Drug Register, excluding randomisation to metformin) |
| Diabetes diagnosis | Estimated follow-up for each patient is 1-4 years | Defined as diabetes diagnosis in National Patient Register and/or prescribed glucose lowering treatment in the Prescribed Drug Register excluding randomisation to metformin in the active treatment arm |
| Time to the composite endpoint CV death, main diagnosis of MI, heart failure or stroke. | Estimated follow-up for each patient is 1-4 years | Time to first event included in the composite endpoint CV death, main diagnosis of MI, heart failure or stroke. |
| Time to the composite endpoint of all-cause death, main diagnosis of MI, stroke and revascularisation (CABG or PCI >4 months after the index AMI). | Estimated follow-up for each patient is 1-4 years | Time to first event included in the composite endpoint of all-cause death, main diagnosis of MI, stroke and revascularisation (CABG or PCI \>4 months after the index AMI). |
| All-cause death | Estimated follow-up for each patient is 1-4 years | Time to all-cause death |
| CV death | Estimated follow-up for each patient is 1-4 years | Time to CV death |
| Hospitalisation with stroke | Estimated follow-up for each patient is 1-4 years | Time to hospitalisation for stroke (main diagnosis) |
| Hospitalisation with heart failure | Estimated follow-up for each patient is 1-4 years | Time to hospitalisation for heart failure (main diagnosis) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Hypoglycaemia | Estimated follow-up for each patient is 1-4 years | Number of events of hypoglycaemia |
| Serious Adverse Events | Estimated follow-up for each patient is 1-4 years | Number of Serious Adverse Events with at least a possible relationship to the study medication |
| Lactic acidosis (E11.1D) | Estimated follow-up for each patient is 1-4 years | Number of events of lactic acidosis |
Countries
Sweden
Contacts
Primary ContactAnna Norhammar, MD, Prof.
Backup ContactViveca Ritsinger, MD, PhD
Outcome results
None listed